In marsupial and eutherian mammals the ratio of active X chromosomes to autosomes is under strict control. In some unknown manner, supernumerary X chromosomes are in part rendered genetically inactive. Various mechanisms have been proposed which purport to describe the X chromosome inactivation process but the data to judge which of these mechanisms is correct has not yet been obtained. To judge these mechanisms, I plan to compare by polyacrylamide gel electrophoresis the chromosomal proteins from human fibroblast cell lines which differ in the number of active and inactive X chromosomes. By comparing the number of chromosomal proteins and amount of each from the different cell lines, I can determine if any of the proteins are specific to either the active or inactive X chromosome. I also plan to isolate the condensed X chromosome and compare the chromosomal proteins and methylated bases of this chromosome to the proteins and methylated bases of other chromatin with similar genetic activity. In this manner, I can determine if similar transcriptional control mechanisms are imposed or if novel transcriptional control mechanisms exist which affect only the inactive X chromosome. Once the proteins of interest have been identified, we can begin to study in greater depth the manner by which a multicistronic block of nonrelated genetic units is regulated independently of its allelic counterpart.